tbuckley/cabot-search huggingface dataset:
CDC Report: Urgent Need to Address Teens’ Adverse Experiences During Pandemic
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
JAK–STAT Signaling in Inflammatory Breast Cancer Enables Chemotherapy-Resistant Cell States
Authors: Laura E. Stevens, Guillermo Peluffo, Xintao Qiu, Daniel Temko, Anne Fassl, Zheqi Li, Anne Trinh, Marco Seehawer, Bojana Jovanović, Maša Alečković, Callahan M. Wilde, Renee C. Geck, Shaokun Shu, Natalie L. Kingston, Nicholas W. Harper, Vanessa Almendro, Alanna L. Pyke, Shawn B. Egri, Malvina Papanastasiou, Kendell Clement, Ningxuan Zhou, Sarah Walker, Jacqueline Salas, So Yeon Park, David A. Frank, Alexander Meissner, Jacob D. Jaffe, Piotr Sicinski, Alex Toker, Franziska Michor, Henry W. Long, Beth A. Overmoyer, Kornelia Polyak
Journal: Cancer Research (2022)

Abstract Inflammatory breast cancer (IBC) is a difficult-to-treat disease with poor clinical outcomes due to high risk of metastasis and resistance to treatment. In breast cancer, CD44+CD24− cells possess stem cell-like features and contribute to disease progression, and we previously described a CD44+CD24−pSTAT3+ breast cancer cell subpopulation that is dependent on JAK2/STAT3 signaling. Here we report that CD44+CD24− cells are the most frequent cell type in IBC and are commonly pSTAT3+. Combination of JAK2/STAT3 inhibition with paclitaxel decreased IBC xenograft growth more than either agent alone. IBC cell lines resistant to paclitaxel and doxorubicin were developed and characterized to mimic therapeutic resistance in patients. Multi-omic profiling of parental and resistant cells revealed enrichment of genes associated with lineage identity and inflammation in chemotherapy-resistant derivatives. Integrated pSTAT3 chromatin immunoprecipitation sequencing and RNA sequencing (RNA-seq) analyses showed pSTAT3 regulates genes related to inflammation and epithelial-to-mesenchymal transition (EMT) in resistant cells, as well as PDE4A, a cAMP-specific phosphodiesterase. Metabolomic characterization identified elevated cAMP signaling and CREB as a candidate therapeutic target in IBC. Investigation of cellular dynamics and heterogeneity at the single cell level during chemotherapy and acquired resistance by CyTOF and single cell RNA-seq identified mechanisms of resistance including a shift from luminal to basal/mesenchymal cell states through selection for rare preexisting subpopulations or an acquired change. Finally, combination treatment with paclitaxel and JAK2/STAT3 inhibition prevented the emergence of the mesenchymal chemo-resistant subpopulation. These results provide mechanistic rational for combination of chemotherapy with inhibition of JAK2/STAT3 signaling as a more effective therapeutic strategy in IBC. Significance: Chemotherapy resistance in inflammatory breast cancer is driven by the JAK2/STAT3 pathway, in part via cAMP/PKA signaling and a cell state switch, which can be overcome using paclitaxel combined with JAK2 inhibitors.
Low-Value Prostate-Specific Antigen Test for Prostate Cancer Screening and Subsequent Health Care Utilization and Spending
Authors: David D. Kim, Allan T. Daly, Benjamin C. Koethe, A. Mark Fendrick, Daniel A. Ollendorf, John B. Wong, Peter J. Neumann
Journal: JAMA Network Open (2022)

Importance Delivering low-value care can lead to unnecessary follow-up services and associated costs, and such care cascades have not been well examined in common clinical scenarios. Objective To evaluate the utilization and costs of care cascades of prostate-specific antigen (PSA) tests for prostate cancer screening, as the routine use of which among asymptomatic men aged 70 years and older is discouraged by multiple guidelines. Design, Setting, and Participants This cross-sectional study included men aged 70 years and older without preexisting prostate conditions enrolled in a Medicare Advantage plan during January 2016 to December 2018 with at least 1 outpatient visit. Medical billing claims data from the deidentified OptumLabs Data Warehouse were used. Data analysis was conducted from September 2020 to August 2021. Exposures At least 1 claim for low-value PSA tests for prostate cancer screening during the observation period. Main Outcomes and Measures Utilization of and spending on low-value PSA cancer screening and associated care cascades and the difference in overall health care utilization and spending among individuals receiving low-value PSA cancer screening vs those who did not, adjusting for observed characteristics using inverse probability of treatment weighting. Results Of 995 442 men (mean [SD] age, 78.0 [5.6] years) aged 70 years or older in a Medicare Advantage plan included in this study, 384 058 (38.6%) received a low-value PSA cancer screening. Utilization increased for each subsequent cohort from 2016 to 2018 (49 802 of 168 951 [29.4%] to 134 404 of 349 228 [38.5%] to 199 852 of 477 203 [41.9%]). Among those receiving initial low-value PSA cancer screening, 241 188 of 384 058 (62.8%) received at least 1 follow-up service. Repeated PSA testing was the most common, and 27 268 (7.1%) incurred high-cost follow-up services, such as imaging, radiation therapy, and prostatectomy. Utilization and spending associated with care cascades also increased from 2016 to 2018. For every $1 spent on a low-value PSA cancer screening, an additional $6 was spent on care cascades. Despite avoidable care cascades, individuals who received low-value PSA cancer screening were not associated with increased overall health care utilization and spending during the 1-year follow-up period compared with an unscreened population. Conclusions and Relevance In this cross-sectional study, low-value PSA tests for prostate cancer screening remained prevalent among Medicare Advantage plan enrollees and were associated with unnecessary expenditures due to avoidable care cascades. Innovative efforts from clinicians and policy makers, such as payment reforms, to reduce initial low-value care and avoidable care cascades are warranted to decrease harm, enhance equity, and improve health care efficiency.
Major depression and the biological hallmarks of aging
Authors: Erica C. Lorenzo, George A. Kuchel, Chia-Ling Kuo, Terrie E. Moffitt, Breno S. Diniz
Journal: Ageing Research Reviews (2022)

Major depressive disorder (MDD) is characterized by psychological and physiological manifestations contributing to the disease severity and outcome. In recent years, several lines of evidence have suggested that individuals with MDD have an elevated risk of age-related adverse outcomes across the lifespan. This review provided evidence of a significant overlap between the biological abnormalities in MDD and biological changes commonly observed during the aging process (i.e., hallmarks of biological aging). Based on such evidence, we formulate a mechanistic model showing how abnormalities in the hallmarks of biological aging can be a common denominator and mediate the elevated risk of age-related health outcomes commonly observed in MDD. Finally, we proposed a roadmap for novel studies to investigate the intersection between the biology of aging and MDD, including the use of geroscience-guided interventions, such as senolytics, to delay or improve major depression by targeting biological aging.
Fluid Bolus Administration and Cardiovascular Collapse in Critically Ill Patients Undergoing Tracheal Intubation
Authors: Nirvik Pal, Miklos D. Kertai, John Butterworth
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Assessment of Uptake Appropriateness of Computed Tomography for Lung Cancer Screening According to Patients Meeting Eligibility Criteria of the US Preventive Services Task Force
Authors: Yu Liu, I-Wen Elaine Pan, Hyo Jung Tak, Ioannis Vlahos, Robert Volk, Ya-Chen Tina Shih
Journal: JAMA Network Open (2022)

Importance Currently, computed tomography (CT) is used for lung cancer screening (LCS) among populations with various levels of compliance to the eligibility criteria from the US Preventive Services Task Force (USPSTF) recommendations and may represent suboptimal allocation of health care resources. Objective To evaluate the appropriateness of CT LCS according to the USPSTF eligibility criteria. Design, Setting, and Participants This cross-sectional study used the 2019 Behavioral Risk Factor Surveillance System (BRFSS) survey. Participants included individuals who responded to the LCS module administered in 20 states and had valid answers to questions regarding screening and smoking history. Data were analyzed between October 2021 and August 2022. Exposures Screening eligibility groups were categorized according to the USPSTF 2013 recommendations, and subgroups of individuals who underwent LCS were analyzed. Main Outcomes and Measures Main outcomes included LCS among the screening-eligible population and the proportions of the screened populations according to compliance categories established from the USPSTF 2013 and 2021 recommendations. In addition, the association between respondents’ characteristics and LCS was evaluated for the subgroup who were screened despite not meeting any of the 3 USPSTF screening criteria: age, pack-year, and years since quitting smoking. Results A total of 96 097 respondents were identified for the full study cohort, and 2 subgroups were constructed: (1) 3374 respondents who reported having a CT or computerized axial tomography to check for lung cancer and (2) 33 809 respondents who did not meet any screening eligibility criteria. The proportion of participants who were under 50 years old was 53.1%; between 50 and 54, 9.1%; between 55 and 79, 33.8%; and over 80, 4.0%. A total of 51 536 (50.9%) of the participants were female. According to the USPSTF 2013 recommendation, 807 (12.8%) of the screening-eligible population underwent LCS. Among those who were screened, only 807 (20.9%) met all 3 screening eligibility criteria, whereas 538 (20.1%) failed to meet any criteria. Among respondents in subgroup 2, being of older age and having a history of stroke, chronic obstructive pulmonary disease, kidney disease, or diabetes were associated with higher likelihood of LCS. Conclusions and Relevance In this cross-sectional study of the BRFSS 2019 survey, the low uptake rate among screening-eligible patients undermined the goal of LCS of early detection. Suboptimal screening patterns could increase health system costs and add financial stress, psychological burden, and physical harms to low-risk patients, while failing to provide high-quality preventive services to individuals at high risk of lung cancer.
Development of Interstitial Lung Disease Among Patients With Atrial Fibrillation Receiving Oral Anticoagulants in Taiwan
Authors: Yi-Hsin Chan, Tze-Fan Chao, Shao-Wei Chen, Hsin-Fu Lee, Wei-Min Chen, Pei-Ru Li, Yung-Hsin Yeh, Chi-Tai Kuo, Lai-Chu See, Gregory Y. H. Lip
Journal: JAMA Network Open (2022)

Importance There are emerging concerns from case reports and pharmacovigilance analyses of a possible risk of interstitial lung disease (ILD) associated with the use of factor Xa (FXa) inhibitors. Objective To evaluate the risk of incident ILD associated with the use of oral anticoagulants (OACs) in patients with nonvalvular atrial fibrillation (NVAF). Design, Setting, and Participants This nationwide retrospective cohort study used data from the Taiwan National Health Insurance Research Database. Patients with NVAF without preexisting lung disease who received OACs from June 1, 2012, to December 31, 2017, were included. Propensity score stabilized weighting (PSSW) was used to balance covariates across the medication groups (FXa inhibitors, dabigatran, and warfarin, with warfarin as the reference). Patients were followed up from the drug index date until the onset of ILD, death, or end of the study (December 31, 2019), whichever occurred first. Data were analyzed from September 11, 2021, to August 3, 2022. Exposures Patients with NVAF were treated with FXa inhibitors, dabigatran, or warfarin. Main Outcomes and Measures New-onset idiopathic ILD. Results Among the 106 044 patients (mean [SD] age, 73.4 [11.9] years; 59 995 men [56.6%]) included in the study, 64 555 (60.9%) received FXa inhibitors (apixban [n = 15 386], edoxaban [n = 12 413], and rivaroxaban [n = 36 756]), 22 501 (21.2%) received dabigatran, and 18 988 (17.9%) received warfarin at baseline. The FXa inhibitors were associated with a higher risk of incident ILD (0.29 vs 0.17 per 100 patient-years; hazard ratio, 1.54 [95% CI, 1.22-1.94]; P &amp;amp;lt; .001), whereas dabigatran was associated with a nonsignificant difference in risk of incident ILD compared with warfarin (reference) after PSSW. The higher risk of incident ILD for FXa inhibitors vs warfarin was consistent with several high-risk subgroups. Conclusions and Relevance Results of this study suggest that FXa inhibitors were associated with lung injury among patients with NVAF who were treated with OACs. Physicians should be vigilant in monitoring for any potential adverse lung outcomes associated with the use of these drugs.
Plasticity of Individual Lung Function States from Childhood to Adulthood
Authors: Gang Wang, Jenny Hallberg, Rosa Faner, Hans-Jacob Koefoed, Simon Kebede Merid, Susanna Klevebro, Sophia Björkander, Olena Gruzieva, Göran Pershagen, Marianne van Hage, Stefano Guerra, Matteo Bottai, Antonios Georgelis, Ulrike Gehring, Anna Bergström, Judith M. Vonk, Inger Kull, Gerard H. Koppelman, Alvar Agusti, Erik Melén
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Recent evidence highlights the importance of optimal lung development during childhood for health throughout life. Objectives: To explore the plasticity of individual lung function states during childhood. Methods: Prebronchodilator FEV1 z-scores determined at age 8, 16, and 24 years in the Swedish population-based birth cohort BAMSE (Swedish abbreviation for Child [Barn], Allergy, Milieu, Stockholm, Epidemiological study) (N = 3,069) were used. An unbiased, data-driven dependent mixture model was applied to explore lung function states and individual state chains. Lung function catch-up was defined as participants moving from low or very low states to normal or high or very high states, and growth failure as moving from normal or high or very high states to low or very low states. At 24 years, we compared respiratory symptoms, small airway function (multiple-breath washout), and circulating inflammatory protein levels, by using proteomics, across states. Models were replicated in the independent Dutch population-based PIAMA (Prevention and Incidence of Asthma and Mite Allergy) cohort. Measurements and Main Results: Five lung function states were identified in BAMSE. Lung function catch-up and growth failure were observed in 74 (14.5%) BAMSE participants with low or very low states and 36 (2.4%) participants with normal or high or very high states, respectively. The occurrence of catch-up and growth failure was replicated in PIAMA. Early-life risk factors were cumulatively associated with the very low state, as well as with catch-up (inverse association) and growth failure. The very low state as well as growth failure were associated with respiratory symptoms, airflow limitation, and small airway dysfunction at adulthood. Proteomics identified IL-6 and CXCL10 (C-X-C motif chemokine 10) as potential biomarkers of impaired lung function development. Conclusions: Individual lung function states during childhood are plastic, including catch-up and growth failure.
Morphine mediated neutrophil infiltration in intestinal tissue play essential role in histological damage and microbial dysbiosis
Authors: Richa Jalodia, Udhghatri Kolli, Regina Gonzalez Braniff, Junyi Tao, Yaa Fosuah Abu, Irina Chupikova, Shamsudheen Moidunny, Sundaram Ramakrishnan, Sabita Roy
Journal: Gut Microbes (2022)

The gut microbial ecosystem exhibits a complex bidirectional communication with the host and is one of the key contributing factors in determining mucosal immune homeostasis or an inflammatory state. Opioid use has been established to induce gut microbial dysbiosis consistent with increased intestinal tissue inflammation. In this study, we investigated the role of infiltrated immune cells in morphine-induced intestinal tissue damage and gut microbial dysbiosis in mice. Results reveal a significant increase in chemokine expression in intestinal tissues followed by increased neutrophil infiltration post morphine treatment which is direct consequence of a dysbiotic microbiome since the effect is attenuated in antibiotics treated animals and in germ-free mice. Neutrophil neutralization using anti-Ly6G monoclonal antibody showed a significant decrease in tissue damage and an increase in tight junction protein organization. 16S rRNA sequencing on intestinal samples highlighted the role of infiltrated neutrophils in modulating microbial community structure by providing a growth benefit for pathogenic bacteria, such as Enterococcus, and simultaneously causing a significant depletion of commensal bacteria, such as Lactobacillus. Taken together, we provide the first direct evidence that neutrophil infiltration contributes to morphine-induced intestinal tissue damage and gut microbial dysbiosis. Our findings implicate that inhibition of neutrophil infiltration may provide therapeutic benefits against gastrointestinal dysfunctions associated with opioid use.
The Need for Targeted Labeling of Machine Learning–Based Software as a Medical Device
Authors: Benjamin A. Goldstein, Maciej A. Mazurowski, Cheng Li
Journal: JAMA Network Open (2022)

William Hsu, PhD; Daniel S. Hippe, MS; Noor Nakhaei, BS; Pin-Chieh Wang, PhD; Bing Zhu, PhD; Nathan Siu, BS; Mehmet Eren Ahsen, PhD; William Lotter, PhD; A. Gregory Sorensen, PhD; Arash Naeim, MD, PhD; Diana S. M. Buist, PhD; Thomas Schaffter, PhD; Justin Guinney, PhD; Joann G. Elmore, MD, MPH; Christoph I. Lee, MD, MS
Intelectin-1 binds and alters the localization of the mucus barrier–modifying bacterium <i>Akkermansia muciniphila</i>
Authors: Juan D. Matute, Jinzhi Duan, Magdalena B. Flak, Paul Griebel, Jose A. Tascon-Arcila, Shauni Doms, Thomas Hanley, Agne Antanaviciute, Jennifer Gundrum, Jessica L. Mark Welch, Brandon Sit, Shabnam Abtahi, Gwenny M. Fuhler, Joep Grootjans, Florian Tran, Stephanie T. Stengel, James R. White, Niklas Krupka, Dirk Haller, Simon Clare, Trevor D. Lawley, Arthur Kaser, Alison Simmons, Jonathan N. Glickman, Lynn Bry, Philip Rosenstiel, Gary Borisy, Matthew K. Waldor, John F. Baines, Jerrold R. Turner, Richard S. Blumberg
Journal: The Journal of Experimental Medicine (2022)

Intelectin-1 (ITLN1) is a lectin secreted by intestinal epithelial cells (IECs) and upregulated in human ulcerative colitis (UC). We investigated how ITLN1 production is regulated in IECs and the biological effects of ITLN1 at the host–microbiota interface using mouse models. Our data show that ITLN1 upregulation in IECs from UC patients is a consequence of activating the unfolded protein response. Analysis of microbes coated by ITLN1 in vivo revealed a restricted subset of microorganisms, including the mucolytic bacterium Akkermansia muciniphila. Mice overexpressing intestinal ITLN1 exhibited decreased inner colonic mucus layer thickness and closer apposition of A. muciniphila to the epithelial cell surface, similar to alterations reported in UC. The changes in the inner mucus layer were microbiota and A. muciniphila dependent and associated with enhanced sensitivity to chemically induced and T cell–mediated colitis. We conclude that by determining the localization of a select group of bacteria to the mucus layer, ITLN1 modifies this critical barrier. Together, these findings may explain the impact of ITLN1 dysregulation on UC pathogenesis.
Covid-19: Is the UK still tracking the virus—and other questions answered
Authors: Elisabeth Mahase
Journal: BMJ (2022)

Covid-19: Is the UK still tracking the virus-and other questions answeredWith the NHS braced for a tough winter, Elisabeth Mahase looks at what's happening with covid tracking and testing, and variants Elisabeth MahaseAre we still tracking covid cases?Although the UK significantly scaled back its covid surveillance earlier this year, 1 the Office for National Statistics' coronavirus infection survey, 2 which involves an online questionnaire and swab and blood samples, and the Real-time Assessment of Community Transmission (REACT-1) study both continue. 3 The ZOE covid study was also given additional funding by the Department of Health and Social Care for England in June this year to continue its work on tracking cases and symptoms.This study relies on a smartphone app in which members of the public can log their symptoms daily.
Trends in the Use of Promotional Language (Hype) in National Institutes of Health Funding Opportunity Announcements, 1992-2020
Authors: Neil Millar, Bojan Batalo, Brian Budgell
Journal: JAMA Network Open (2022)

This cross-sectional study examines changes from 1992 to 2020 in the use of promotional language in National Institutes of Health (NIH) funding opportunity announcements in comparison with trends reported in NIH grant applications.